In the past 20 years, the physiology of pituitary function has become better understood. The pituitary gland secretes several hormones which in turn control secretion of other glands such as the adrenal, the thyroid, and the reproductive organs. In recent times, a series of pituitary releasing hormones have been discovered, and characterized. The most recent of these is growth hormone releasing factor GRF(1-44)-NH.sub.2. This discovery occurred in 1982 when two investigators independently, but almost simultaneously, reported the presence of a substance occurring in a pancreatic tumor which caused a clinical syndrome called acromegaly. In their respective journal articles, they reported that the tumors were found to contain a peptide consisting of 44 amino acids, which when purified and injected into animals or humans was found to stimulate growth hormone production intensively, Science, Vol. 218, Nov. 5, 1982, pp. 585-87 and Nature, Vol. 300, Nov. 18, 1982, pp. 276-78. Recently, some researchers have successfully, synthetically synthesized growth hormone releasing factor, and very recently it has been produced by genetic engineering procedures using bacterial cultures. For literature relating to synthetic production of growth hormone releasing factor, see Gelato, M. C. et al., 1983, "The Effects of Growth Hormone Releasing Factor in Man," Journal of Clinical Endrocrinology and Metab., 57674.
Growth hormone releasing hormone factor is a peptide of 44 amino acids. There are analogs containing 27-40 amino acids. It is one of a group of peptides secreted by the hypothalamus, and it normally stimulates pituitary growth hormone release. It is important in normal growth and development during childhood.
Recently, it has been reported that GRF(1-44)-NH.sub.2 may have some promise in the treatment of growth hormone deficiency (see Journal of Clinical Endrocrinoloqy and Metab., 59:1, 1984 and Journal of Clinical Endrocrinoloqy and Metab., 58:1043, 1984). However, GRF(1-44)-NH.sub.2 has not been marketed or suggested for any specific clinical disease treatment. It has been suggested as likely to be useful for testing pituitary function by using doses to stimulate pituitary secretion of growth hormone. The theory being that in the event it does not so stimulate, one knows that the pituitary gland is not functioning properly. However, when used to test pituitary function, GRF(1-44)-NH.sub.2 is administered intravenously by a single bolus injection and blood levels of growth hormone are measured in serum specimens obtained at approximately half hour intervals for four hours. If growth hormone levels fail to rise, then the presumption is made that the pituitary gland is incapable of secreting growth hormone. This is a single dose for diagnostic purposes, not a periodic and regular treatment pattern.
Postmenopausal osteoporosis is defined as the presence of severe loss of bone, with or without fractures, in women who are past menopause. Bone loss without fractures has been termed osteopenia, although many refer to bone loss with or without fractures as osteoporosis. The bone loss is from the "inside" of the skeleton rather than a shrinkage of the outer volume of the skeleton. The skeleton "hollows out." For many years, physicians have been searching for an agent that will cause reaccumulation of this lost bone so that risk of fracture is diminished. It is a major public health problem affecting millions of postmenopausal women. Almost half of the Caucasian women in the United States can be expected to suffer fractures from osteoporosis before they die.
The invention of my two prior patents dealt with the treatment of osteoporosis, preferably postmenopausal osteoporosis with GRF(1-44)-NH.sub.2 until the patient's bone mass increases and the patient's calcium balance becomes positive, indicating mineral accumulation in the skeleton, see Recker U.S. Pat. Nos. 4,710,382 issued Dec. 1, 1987 and U.S. Pat. No. 4,870,054, issued Sep. 26, 1989.
One particular problem with postmenopausal females is that the loss of skeletal mass is most heavy in the hip and spine. Thus, with a process such as that described in my previous two patents, while such is extremely helpful for postmenopausal patients, it would be desirable if bone mass was increased particularly in the local area of the hip and spine at a faster rate than for the rest of the patient's skeleton. Put another way, since bone mass has deteriorated most in the area of the hip and spine in many postmenopausal females, if needed, it would be desirable to increase the mineral accumulation in these areas at a faster rate in order to compensate for the greater loss.
It is, therefore, a primary objective of the present invention to provide a method of treatment of postmenopausal osteoporosis which not only overall increases patient bone mass but increases bone mass in a manner that is particularly suitable for patient treatment where the loss has been significant in the hip and spine.
Another objective of the present invention is to provide a method of treatment of postmenopausal osteoporosis which can be used in combination with the method of my earlier patents using GRF(1-44)-NH.sub.2 or a biologically acceptable analog thereof to synergistically increase bone mass in the hip and spine area.
Another objective of the present invention is to provide a method of successfully administering GRF(1-44)-NH.sub.2 or biologically acceptable analogs thereof concurrently with parathyroid hormone (PTH(1-34)-NH.sub.2) or biologically acceptable analogs thereof, with the combination enhancing the effect in reversing bone mass loss in postmenopausal patients beyond that which can be achieved by administering either individually.
A still further objective of the present invention is to provide a nasal insufflation composition which can be used in a combined treatment protocol for a synergistic treatment of osteoporosis.
The method and means of accomplishing each of the above objectives, as well as others, will become apparent from the description of the invention which follows hereinafter.
It goes without saying that certain modifications to the growth hormone releasing factor itself, or to the composition containing the same, may be made without department from the spirit or scope of the present invention. Put another way, modifications both in the formula to provide some related analogs of the growth release factor, and in the composition to provide either other forms of administration, or other pharmaceutically acceptable related compositions may be made. These modifications are included in the scope of this invention.